Are You Fair When Designing Your Oncology Trials? (Guest blog)
01.06.22
In June 2020, EFPIA and other trade associations - Biotechnology Innovation Organization (BIO), European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), the European Association of Bioindustries (EuropaBio) and the Pharmaceutical Research Manufacturers of America (PhRMA) – released a Letter of Support to the ACCELERATE FAIR Initiative. A similar support was also provided by EU and US regulators and the EFGCP (European Forum for Good Clinical Practice), which show how the efforts led by the ACCELERATE’S FAIR Initiative are recognised and valued.
Until recently, research into adolescents and young adults’ with cancer has made slower progress than for any other age group, mainly because patients under 18 were excluded from participation in adult trials. To address the issue, the ACCELERATE[1] Forum established a Working Group on Fostering Age Inclusive Research (or FAIR Trials; https://www.accelerate-platform.org/fair-trials). Including experts from Academia, Industry and Parents/Patients advocacy, the initiative led by Dr Nathalie Gaspar (Institut Gustave Roussy, France) and Chris Copland (Patient representative, NCRI - National Cancer Research Institute, UK) aims at raising awareness and promoting a change.
With the goal of facilitating timely access to novel therapies for children with cancer, the FAIR Initiative is seen as an important step to encourage researchers, regulators, ethics committees, and Health Technology Assessment (HTA) bodies to support and consider the systematic inclusion of adolescents (i.e., individuals from 12 to less than 18 years of age), in oncology studies based on the benefit-risk profile of a product, when scientifically, ethically justified and feasible.
Involving adolescents in adult studies has been advocated by regulators since 2000 with the release of the ICH E11 Paediatric guideline. Since then, this international guideline was revisited and then complemented with the release in 2019 of a US FDA guidance on the Inclusion of Adolescents Patients in Adult Oncology Clinical Trials. The involvement of adolescents in adult trials can also considered beyond oncology, where scientifically justified. However in a review performed by the European Forum for Good Clinical Practice (EFGCP) Children Medicines Working Party, a multi-stakeholder workgroup focused on contributing to ethical, scientific, legal, safety and societal issues related to the design, conduct, analysis and reporting of biomedical research and development of new medicines for children of all ages, existing US and EU disease guidelines contain limited discussion on the role for adolescent inclusion (Bucci-Rechtweg C, 2022). Hence, the call for actions of this group, to address content gaps within existing guidance that could enhance pediatric medicines development for adolescents. Similarly, stakeholders (e.g., adult and pediatric trialists, industry, ethics committees, regulators) should work together to facilitate the evolution of regulatory thinking on adolescent inclusion in adult trials and/or the conduct of adolescent trials in parallel to the adult program.
While it may be possible to include adolescents in adult studies, it is recognised that such trials may be challenging to operationalise. In addition, it is not only a change in the mindset of the researchers, but also the need to identify centres knowledgeable and skilled in the care of both adults and adolescents. To address these challenges, the FAIR work group has issued a FAIR Investigators’ Tool Kit which provides useful information to help sponsors designing and performing such trials, including Assent templates or a list of AYA-clinical referee by countries. More recently, FAIR has proposed a 6-point approach in order to improve access for adolescents to new anti-cancer drugs and to make drug development more efficient (Gaspar et al. Annals of Oncology, 2018).
The FAIR initiative has recently introduced the FAIR for AYA STAMP, a tool intended to acknowledge trials which actively implement age-inclusive trial methods to avoid unnecessary barriers to trial participation based on age. It is hoped that the FAIR STAMP will encourage other researchers and trial sponsors to offer opportunities for adolescents and young adults to participate in oncology trials.
ACCELERATE is kindly supported by the Andrew McDonough B+ Foundation
[1] ACCELERATE brings together academia, industry, advocacy and regulators to find solutions for more and better innovative therapies for children and adolescents with cancer (About us | ACCELERATE Platform (accelerate-platform.org).
